We had earlier suggested a mechanism for the origin of frameshift mutations. We now propose tests for our model, and will attempt to relate the frequency of mutation to the base sequence at the site of the mutation. In addition, we propose to determine how certain features of the base sequence influence the frequency of transition mutation. Mutations in the bacteriophage T4 lysozyme will be examined; the frequency of mutation will be determined by selective methods that have been developed, while the base sequence will be examined by the analysis of amino acid replacements. In our model for the origin of frameshift mutations, additions or deletions of bases occur through the mis-alignment of short stretches of bases at sites in the DNA which contain repeating bases or base doublets and which are bounded on one side by a single stranded gap. In one set of proposed experiments the frequencies of the deletion and addition of a base pair will be measured at a particular site at which the number of identical sequential base pairs is varied from four to six; in another set of experiments the base sequences of mutated sites with unusually high reversion frequencies will be determined. We propose that transition mutations occur with a relatively low frequency during the synthesis of stretches of purines, as compared to higher frequencies during the synthesis of stretches of pyrimidines or mixed purines and pyrimidines. We intend to test this idea by measuring 2-aminopurine and 5-bromouracil-induced mutation frequencies from tryptophan to amber and from amber to tryptophan at various sites in the lysozyme gene of bacteriophage T4.